Angiogenesis (the formation of new blood vessels) is an important process in tumor growth, wound healing, retinopathies, and rheumatoid arthritis. We are investigating aspects of angiogenesis in an in vitro model utilizing isolated human and bovine endothelial cells and a mixture of basement membrane matrix proteins (Matrigel). Plating endothelial cells on Matrigel-coated tissue culture dishes led to their rapid (12 to 18 hr) organization into a capillary-like network. Normally endothelial cells are quiescent in vivo; but in response to an angiogenic factor, activated endothelial cells will breakdown their underlying basement membrane, migrate into the interstitium, proliferate, and finally differentiate into a new blood vessel. We found that quiescent endothelial cells (contact inhibition or serum starvation) were not able to organize into a capillary-like network in vitro, while cells released from contact inhibition or feed serum-containing media regained the ability to organize. There was a correlation between the ability to organize on Matrigel and the expression of cell surface receptors for the basement membrane proteins, laminin and collagen IV. These studies should prove useful in studying some early events involved in angiogenesis. Often angiogenic factors attract leukocytes and fibroblast, while stimulating the formation of new blood vessels. Previous studies have demonstrated that leukocytes can release angiogenic factors, but it is unclear whether fibroblast cells may also be involved. We tested whether fibroblasts may produce factors that alter endothelial cell function. We found that fibroblast-conditioned media increased endothelial cell proliferation, contained a cellular attractant, and enhanced the extent of capillary-like formations on the Matrigel. The ability of fibroblasts to influence angiogenesis may be an important component of wound-healing.